TRICS 3: Restrictive Transfusion Appears Safe in CV Surgery

August 28, 2018

MUNICH — New research suggests that patients undergoing cardiac surgery may not need a blood transfusion as soon as their blood hemoglobin (Hgb) levels fall below around 8.5 or 9.5 g/dL, and instead, this can wait until the levels drop further.

Specifically, among patients with a moderate or higher risk of dying from cardiac surgery, those who received a blood transfusion only when their blood hemoglobin levels fell below 7.5 g/dL (restrictive strategy) did not have worse 6-month outcomes than those who received a transfusion at a higher hemoglobin level (liberal strategy).

The goal was to see whether a restrictive transfusion strategy during cardiac surgery was safe and noninferior compared with a liberal transfusion strategy, C. David Mazer, MD, from St. Michael's Hospital, Toronto, Ontario, Canada, told theheart.org | Medscape Cardiology.

He presented the 6-month findings from the Transfusion Requirements in Cardiac Surgery (TRICS) 3 trial here at the European Society of Cardiology (ESC) Congress 2018, and the results were simultaneously published August 25 in the New England Journal of Medicine.

"The question was, 'When do the risks of transfusion outweigh the risks of anemia?"' he said. "It would better to avoid both, but is a threshold of hemoglobin 7.5 g/dL safe?"

In fact, the study showed that a restrictive strategy for red cell transfusion was noninferior to a liberal strategy with respect to the primary composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, at 6 months after surgery.

Preliminary 28-day results from TRICS3, which were presented last November and reported at that time by theheart.org | Medscape Cardiology, were similar.

Together, the two sets of results show "there is no harm in adopting" a restrictive transfusion strategy during heart surgery, the assigned discussant at the presentation session, Miguel Sousa-Uva, MD, PhD, from Hospital Cruz Vermetha, Lisbon, Portugal, said in an emailed comment.

"There is conflicting evidence," he noted, but a restrictive strategy is gaining momentum as being noninferior even at 6 months, "and therefore as a default, it makes clinical and economic sense."

Interestingly, in a subgroup analysis, patients aged 75 years and older seemed to have better outcomes with a restrictive transfusion strategy, and younger patients seemed to do better with a liberal transfusion strategy.

But while this finding is "intriguing," it is only hypothesis generating at the moment, Mazer cautioned.

5000 Patients in 19 Countries

Most guidelines recommend that patients undergoing cardiac surgery should have as transfusion if their hemoglobin falls to 7 or 8 g/dL, Mazer explained.

Moreover, according to the guidelines, there seems to be no advantage to transfuse patients whose hemoglobin levelis 10 g/dL or higher, no matter what their condition is, he added.

But, said Mazer, it's the area between 7 or 8 and 10 g/dL "that has been so uncertain, that we were studying."

Transfusion may cause immunologic, infection, or volume side effects, he noted, but on the other hand, anemia can lead to persistent, harmful tissue hypoxia.

TRICS-3 was a large randomized trial conducted at 74 sites in 19 countries on all continents except Antarctica. The researchers randomly assignes 4860 adults undergoing cardiac surgery to have surgery with a restrictive transfusion strategy or surgery with a liberal transfusion strategy.

The patients also had to have a moderate or higher risk of dying from the surgery — defined as a preoperative EuroSCORE of 6 or higher on a scale from 0 (best) to 47 (worst) — based on age, type, and urgency of the cardiac surgery, and preexisting conditions, including myocardial infarction, heart failure, cerebrovascular disease, or pulmonary disease.

Patients in both groups had a mean age of 72 years, and 64% were men.

They underwent one of several different types of cardiac surgery: CABG only (26%), CABG and valve surgery (19%), CABG and nonvalve surgery (8%), valve surgery only (29%), and other non-CABG surgery (18%).

Patients in the restrictive red cell transfusion strategy group received a transfusion if their hemoglobin was less than 7.5 g/dL during or after surgery.

Patients in the liberal red cell transfusion strategy group received a transfusion if their hemoglobin was less than 9.5 g/dL when they were being cared for in the intensive care unit (ICU) or was less than 8.5 g/dL when they were in a non-ICU ward.

Cost Savings, Age Differences Need Further Study

At 6 months, the primary composite outcome occurred in 17.4% of patients in the restrictive-threshold group vs 17.1% of patients in the liberal-threshold group (P = .006 for noninferiority).

The mortality rate was similar in both groups: 6.2% and 6.4% in the restrictive and liberal threshold groups, respectively.

There were no significant between-group differences in the secondary outcomes, which included the individual components of the primary outcome as well as emergency department visits, hospital readmission, or coronary revascularization.

Patients in the restrictive transfusion strategy group received significantly less blood than patients in the liberal group, and significantly fewer of those patients received a blood transfusion.

A "back-of-the-envelope" calculation suggested that this resulted in a cost saving of $2.5 to 3 million, assuming that the activity-based cost of a unit of blood is about $1000, said Mazer.

The finding that older patients fared better with the restrictive transfusion strategy goes against traditional thinking that older patients are probably better off having a high hemoglobin at transfusion compared with younger people.

"This is a curious finding," he continued, and although it was consistent in the 28-day and 6-month outcomes, it requires further study.

The study was supported by grants from grants from the Canadian Institutes of Health Research. The disclosures of the authors are listed with the article.